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Home , Budesonide, Ciclesonide, Flunisolide, Fluticasone, Fluticasone furoate, Fluticasone propionate

Therapeutic Class Overview Intranasal

INTRODUCTION  Intranasal corticosteroids are primarily used to treat perennial allergic (PAR) and seasonal (SAR) and may be useful in the treatment of some forms of nonallergic rhinitis (Wallace et al, 2008).  Symptoms associated with allergic rhinitis include , , sneezing and/or nasal itching. These symptoms result from a complex -driven mucosal caused by resident and infiltrating inflammatory cells and a number of vasoactive and proinflammatory mediators (Wallace et al, 2008).  Treatment should consist of patient education, allergen avoidance activities and pharmacological therapies. Patients should be educated on how to avoid known triggers, such as aeroallergens, dust mites, molds and irritants whenever possible. In addition to environmental control measures, pharmacological therapies may be used to control symptoms.  Intranasal corticosteroids down-regulate the inflammatory response by binding to the intracellular receptors of inflammatory cells and causing a conformational change, thereby controlling the rate of protein synthesis and suppressing the transcription of and chemokine genes (Clinical Pharmacology®, 2017).  Most intranasal corticosteroids are approved by the Food and Drug Administration (FDA) for the treatment of PAR and SAR. (NASONEX®) carries an additional indication for the prophylaxis of SAR. NASACORT 24HR® ( acetate), FLONASE® ALLERGY RELIEF ( propionate), FLONASE® SENSIMIST ALLERGY RELIEF (), and RHINOCORT® ALLERGY () are all FDA-approved for over- the-counter use (Drugs@FDA, 2017).  Nasal polyposis is an inflammatory condition of the nasal and sinus mucosa and usually presents as persistent nasal obstruction (Wallace et al, 200flu8). Two currently available intranasal corticosteroids, beclomethasone (BECONASE AQ®) and mometasone (NASONEX®) are also FDA-approved for the management of nasal polyps.  Beclomethasone (BECONASE AQ) and are approved for the management of nonallergic rhinitis (eg, infectious rhinitis, hormonal rhinitis and vasomotor nonallergic rhinitis with eosinophilia syndrome). Unlike allergic rhinitis, nonallergic rhinitis is characterized by periodic or perennial symptoms that are not a result of immunoglobulin E-dependent events (Wallace et al, 2008).  Beclomethasone (QNASL™) and (ZETONNA®) are the only two intranasal products formulated as a “dry” nasal aerosol; all other products within the class are formulated as aqueous suspensions.  Recently, VERAMYST® (fluticasone furoate) was withdrawn from the market after over-the-counter FLONASE® SENSIMIST™ ALLERGY RELIEF (fluticasone furoate) was launched (GlaxoSmithKline press release, 2017; Snyder- Bulik, 2017).  Continuous administration of intranasal corticosteroids is more efficacious than as-needed dosing, and the onset of therapeutic effect occurs between three and twelve hours (Wallace et al, 2008).  As a result of both the and the relatively low systemic of these agents, intranasal corticosteroids are generally not associated with any clinically significant systemic adverse events. Moreover, drug interactions are limited when administered at recommended doses. The most common adverse events include nasal irritation and mild epistaxis.  The agents included in this review are listed in Table 1 by brand name. Since there are some branded agents that contain the same generic component, the remaining tables in the review are organized by generic name.  Medispan Class: Nasal

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Table 1. Included Within Class Review Manufacturer FDA Approval Date Availability BECONASE AQ (beclomethasone GlaxoSmithKline 07/27/1987 - dipropionate monohydrate) FLONASE ALLERGY RELIEF† (fluticasone GlaxoSmithKline 07/23/2014  propionate) FLONASE SENSIMIST ALLERGY RELIEF† GlaxoSmithKline 08/02/2016 - (fluticasone furoate) * Various 09/24/1981  fluticasone propionate* Various 10/19/1994  NASACORT ALLERGY 24HR† (triamcinolone 10/11/2013  acetonide) NASONEX (mometasone furoate Merck Sharp Dohme 10/01/1997  monohydrate) OMNARIS® (ciclesonide) Sunovion 11/21/2007 - QNASL (beclomethasone dipropionate) Teva Branded Pharm 03/23/2012 - RHINOCORT ALLERGY† (budesonide) McNeil Consumer 03/23/2015  Healthcare RHINOCORT AQUA (budesonide) AstraZeneca 10/01/1999  triamcinolone* Various 05/20/1996  ZETONNA (ciclesonide) Sunovion 01/20/2012 - *Brand prescription FLONASE (fluticasone propionate), NASALIDE (flunisolide), and NASACORT AQ (triamcinolone) are no longer marketed; however, generics for these products are available. †Over-the-counter product (Drugs@FDA, 2017; Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations, 2017; Drug Facts and Comparisons, 2017)

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INDICATIONS Table 2. Food and Drug Administration-Approved Indications

Indication (OTC) (OTC) (OTC) (OTC) furoate propionate propionate propionate propionate Flunisolide Fluticasone Fluticasone Fluticasone Fluticasone Fluticasone Ciclesonide Ciclesonide Budesonide Budesonide Budesonide Mometasone Mometasone furoate (OTC) Triamcinolone Triamcinolone Triamcinolone Triamcinolone Beclomethasone Beclomethasone Indications for Prescription Products    Treatment/relief of symptoms of SAR and PAR (age (age (age ≥6)* ≥12)† ≥2)       Treatment of nasal symptoms of SAR (age (age (age (age (age (age ≥4)‡ ≥6) ≥6)§ ≥6) ≥2) ≥2)       Treatment of nasal symptoms of PAR (age (age (age (age (age (age ≥4)‡ ≥6) ≥12)§ ≥6) ≥2) ≥2)  Treatment/relief of nasal congestion associated (age with SAR ≥2)  Prophylaxis of nasal symptoms of SAR (age ≥12)  Relief of symptoms of nonallergic (vasomotor) (age rhinitis ≥6)*  Management of nasal symptoms of perennial (age nonallergic rhinitis ≥4)  Treatment of nasal polyps (age ≥18)  Prevention of recurrence of nasal polyps following (age surgical removal ≥6)*

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OTC Uses Temporary relief of symptoms of hay fever or other   upper respiratory : nasal congestion, (age (age runny nose, sneezing, and itchy nose ≥6) ≥2) Temporary relief of symptoms of hay fever or other   upper respiratory allergies: nasal congestion, (age (age

runny nose, sneezing, itchy nose, and itchy, ≥2)║ ≥4) watery eyes OTC = over-the-counter *Beconase AQ †Zetonna ‡Qnasl §Omnaris ║Itchy, watery eyes use is for patients ≥12 years of age

(Prescribing information: BECONASE AQ, 2015; FLONASE ALLERGY RELIEF, 2015; FLONASE SENSIMIST, 2017; flunisolide, 2016; fluticasone propionate, 2017; NASACORT ALLERGY 24HR, 2016; NASONEX, 2013; OMNARIS, 2016; QNASL, 2016; RHINOCORT ALLERGY, 2016; RHINOCORT AQUA, 2016; triamcinolone, 2013; ZETONNA, 2014)

Information on indications, mechanism of action, , dosing, and safety has been obtained from the prescribing information for the individual products, except where noted otherwise.

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CLINICAL EFFICACY SUMMARY  Daily administration of intranasal corticosteroids is associated with statistically significant improvements in allergy- related total nasal symptom score (TNSS) and health related quality of life scores. Numerous head-to-head clinical trials comparing the available intranasal corticosteroids have generally demonstrated no significant clinical differences among the available intranasal corticosteroids with regard to efficacy. Some studies have reported differences in sensory perceptions and patient preference with one agent compared to another. Patients administering the agents noted differences in odor, aftertaste, and severity of irritation, though these differences were not associated with differences in efficacy between the agents (Aasand et al, 1982; Al-Mohaimeid, 1993; Andersson et al, 1995; Bachert et al, 2002; Bachert et al, 2004; Berger et al, 2003; Day et al, 1998; Drouin et al 1996; Graft et al, 1996; Gross et al, 2002; Haye et al, 1993; Hebert et al, 1996; Khanna et al, 2005; LaForce et al, 1994; Langrick, 1984; Lumry et al, 2003; Mak et al, 2013; Mandl et al, 1997; McAllen et al, 1980; McArthur, 1994; Meltzer et al, 2005; Meltzer et al, 2008; Meltzer et al, 2010; Naclerio et al, 2003; Ratner et al, 1992; Sahay et al, 1980; Shah et al, 2003; Sipila et al, 1983; Small et al, 1997; Stern et al, 1997; Stokes et al, 2004; Svendsen et al, 1989; Van As et al, 1993; Vanzieleghem et al, 1987; Varshney et al, 2012; Welsh et al, 1987; Winder et al, 1993, Yonezaki et al, 2016).  Head-to-head trials evaluating the efficacy and safety of beclomethasone, fluticasone propionate and flunisolide demonstrate that these agents are comparable to other agents within the class. However, additional results of these studies reinforce that all of the intranasal corticosteroids should be considered equally efficacious (Aasand et al, 1984; Bachert et al, 2004; Berger et al, 2003; Drouin et al, 1996; Mak et al, 2013; McAllen et al, 1980; Meltzer et al, 2010; Meltzer et al, 2008; Ratner et al, 1992; Sahay et al, 1980; Sipila et al, 1983; Small et al, 1997; Stokes et al, 2004; Van As et al, 1993).  To date, the newly approved intranasal corticosteroid aerosol formulations have been demonstrated to be significantly more effective compared to placebo. In a six-week study of patients with PAR, aerosolized beclomethasone significantly improved reflective TNSS compared to placebo (-2.46 vs -1.63; P<0.001). Furthermore, beclomethasone was associated with a statistically significant improvement in quality of life score compared to placebo (P=0.001) (Meltzer et al, 2012). A two-week study of beclomethasone nasal aerosol 80 µg daily in pediatric patients 6 to 11 years of age with SAR also demonstrated improvement in reflective TNSS compared to placebo (-1.9 vs -1.2; P<0.001) (Storms et al, 2013). A 12-week study of beclomethasone nasal aerosol 80 µg daily in pediatric patients 4 to 11 years of age with perennial allergic rhinitis demonstrated improvement in both reflective and instantaneous TNSS compared to placebo (mean treatment difference -0.53 [P=0.009] and -0.52 [P=0.008], respectively) (Berger et al, 2015).  The aerosolized ciclesonide formulation has also been shown to significantly improve symptoms of allergic rhinitis compared to placebo. In a study by Ratner et al, ciclesonide administered at a daily dose of 80 µg or 160 µg reduced reflective TNSS by 15.1 and 16%, respectively, compared to 3.7% in the placebo group (P<0.001 for both). In addition, significant improvements were observed with both doses of ciclesonide compared to placebo with regard to ocular symptom scores and quality of life (P<0.001 for both). Similar improvements in outcomes were reported in additional studies of up to 26 weeks duration (Berger et al, 2012; LaForce et al, 2009; Mohar et al, 2012; Ratner et al, 2010; Ratner et al, 2012).  A systematic review of 40 studies evaluated the use of topical corticosteroids in the treatment or prevention of recurrence of nasal polyps. Topical corticosteroids were effective compared to placebo in the improvement in overall symptoms, nasal obstruction, and a reduction in the size of polyps. Additionally, topical corticosteroids prevented the regrowth of polyps following surgery. No differences in adverse events between topical corticosteroids and placebo were observed (Kalish et al, 2012).  The Agency for Healthcare Research and Quality (AHRQ) published a comparative effectiveness review of pharmacological therapies for the treatment of SAR. A total of 59 randomized controlled trials met inclusion criteria to compare agents of six classes for relative efficacy. Agents included oral and nasal and , intranasal corticosteroids, modifiers, cromolyn, ipratropium, and normal . Overall, there was insufficient evidence to draw a conclusion about relative efficacy among most of the agents used for the treatment of SAR. For a few comparisons, sufficient evidence was available to draw a conclusion. Oral selective antihistamines and were equivalent for efficacy in reducing nasal and eye symptoms. Montelukast was superior to oral selective antihistamines for controlling symptoms. Based on evidence, intranasal antihistamines and intranasal corticosteroids had equivalent efficacy for nasal and eye symptoms. Similarly, montelukast was comparable to intranasal corticosteroids for nasal symptoms. The combination of intranasal antihistamines and intranasal corticosteroids demonstrated equivalent efficacy in nasal and eye symptom resolution compared to either monotherapy. No information was available about the use of these agents for the treatment of SAR in pregnant women. For children, conclusions about relative efficacy were not determined due to insufficient evidence (Glacy et al, 2013). Data as of May 22, 2017 YP-U/KS-U/LMR Page 5 of 14

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 A meta-analysis evaluated nasal corticosteroids, sublingual allergen immunotherapy (SLIT), second generation H1- antihistamines, combination hydrochloride with fluticasone propionate , and montelukast for the treatment of SAR. By indirect comparison, nasal corticosteroids and grass pollen SLIT tablets had a greater relative clinical impact on symptom scores compared to azelastine hydrochloride combined with fluticasone propionate nasal spray, second generation H1-antihistamines, and montelukast (Devillier et al, 2014). In a similar indirect, meta- analysis, SLIT (timothy grass and ragweed) and mometasone furoate improved TNSS to a greater extent than montelukast and in the treatment of both SAR and PAR (Durham et al, 2016).  A meta-analysis compared the effects of intranasal corticosteroids for treatment of chronic rhinosinusitis. A total of 9 randomized controlled trials were included. There was no evidence that one intranasal spray was more effective than another for disease severity or disease-specific quality of life. Epistaxis was more common with higher doses compared to lower doses (Chong et al, 2016).  Intranasal corticosteroids are considered first-line agents for the treatment of allergic rhinitis, especially for patients with moderate to severe symptoms. Consensus guidelines do not recommend the use of one intranasal corticosteroid product over another. Intranasal corticosteroids combined with intranasal antihistamines are considered to be more effective than either alone in the treatment of allergic rhinitis. Addition of oral antihistamines is not effective (Brozek et al, 2010; Seidman et al, 2015; Snellman et al, 2013; Wallace et al, 2008).

SAFETY SUMMARY  The intranasal corticosteroids are contraindicated in patients with an untreated of the nasal mucosa.  Intranasal corticosteroids should not be used in patients with recent nasal septal ulcers, nasal surgery or trauma, as they may impair wound healing.  Systemic corticosteroid effects such as hypercorticism and adrenal suppression may occur when intranasal steroids are used at higher-than-recommended doses or in susceptible individuals at recommended doses. Patients using corticosteroids may be more susceptible to infection; specific effects of the dose, route and duration of use are not known.  However, as a result of both the route of administration and the relatively low systemic bioavailability of these agents, intranasal corticosteroids are generally not associated with any clinically significant systemic adverse events. Moreover, drug interactions are limited when administered at recommended doses. The most common adverse events include nasal irritation and mild epistaxis. (Drug Facts and Comparisons, 2017)

DOSING AND ADMINISTRATION Table 3. Dosing and Administration Usual Dosage Form: Usual Recommended Administration Drug Recommended Strength Adult Dose Considerations Pediatric Dose Beclomethasone Aerosol for nasal PAR, SAR: Nasal polyps, Suspension: (BECONASE AQ, (QNASL): Aerosol: 320 μg daily, nonallergic The unit should QNASL) 40 μg/actuation (60 administered as two (vasomotor) rhinitis, be primed by actuations) & 80 actuations (80 μg PAR, SAR in releasing six μg/actuation (120 strength) in each nostril children 6 to 12 sprays before actuations) once daily years old: initial use. Suspension: initial, If the pump is Suspension for Suspension: one to two one inhalation in not used for nasal inhalation sprays in each nostril each nostril twice seven days, it (BECONASE AQ): twice daily daily; maximum, should be re- 42 μg/inhalation two in primed until a (180 sprays) Nasal polyps, each nostril twice fine spray nonallergic (vasomotor) daily appears. rhinitis: Suspension: one to two PAR, SAR in Aerosol: The sprays in each nostril children 4 to 11 unit should be twice daily years of age: primed by Aerosol: 80 μg releasing four daily, administered sprays before

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Usual Dosage Form: Usual Recommended Administration Drug Recommended Strength Adult Dose Considerations Pediatric Dose as one actuation initial use. If not (40 μg strength) in used for seven each nostril once days, it should daily be re-primed by releasing two sprays. Budesonide Rx suspension PAR, SAR: PAR, SAR in The unit should (RHINOCORT (RHINOCORT Rx suspension: one children 6 to 12 be primed by ALLERGY, AQUA): 32 spray in each nostril years old: releasing eight RHINOCORT μg/inhalation (120 once daily; maximum, Rx suspension: one sprays before AQUA) sprays) four sprays in each spray in each initial use. If not nostril once daily nostril once daily; used for two OTC suspension maximum, two consecutive (RHINOCORT Hay fever or other upper sprays in each days, it should ALLERGY): 32 respiratory allergies: nostril once daily be re-primed μg/inhalation (60 or OTC suspension: two with one spray 120 sprays) sprays in each nostril Hay fever or other or until a fine once daily; once upper respiratory spray appears. symptoms improve, allergies in children reduce to one spray in 6 to 12 years old: each nostril once daily OTC suspension: one spray in each nostril once daily; maximum, two sprays in each nostril once daily Ciclesonide Aerosol for nasal PAR, SAR: SAR in children ≥6 Suspension: (OMNARIS, inhalation Aerosol: one inhalation years old: The unit should ZETONNA) (ZETONNA): in each nostril once daily Suspension: two be primed by 37 μg/actuation sprays in each releasing eight (60 actuations) Suspension: two sprays nostril once daily sprays before in each nostril once daily initial use. If not Suspension for used for four nasal inhalation consecutive (OMNARIS): days, it should 50 μg/inhalation be re-primed (120 sprays) with one spray or until a fine mist appears.

Aerosol: The unit should be primed by actuating three times before initial use. If not used for ten consecutive days, it must be re-primed by actuating three times.

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Usual Dosage Form: Usual Recommended Administration Drug Recommended Strength Adult Dose Considerations Pediatric Dose Flunisolide Suspension for PAR, SAR: PAR, SAR in The unit should nasal inhalation: Suspension: two sprays children six to 14 be primed 25 μg/inhalation in each nostril twice years old: before initial use (200 sprays) daily; maximum, eight Suspension: one by releasing five sprays in each nostril spray in each or six sprays. It per day nostril three times must be re- daily or two sprays primed if it has in each nostril twice not been used daily; maximum, for five days or four inhalations in more, or if it has each nostril per day been disassembled for cleaning. Fluticasone furoate OTC suspension for Hay fever or other upper Hay fever or other OTC (FLONASE nasal inhalation respiratory allergies: upper respiratory suspension: The SENSIMIST) (FLONASE OTC suspension: two allergies in children unit should be SENSIMIST): 27.5 sprays in each nostril 2 to 11 years of primed before μg/inhalation (30, once daily for one week; age: initial use, when 60, or 120 sprays) maintenance, one or two OTC suspension: not used for 30 sprays in each nostril one spray in each days or longer, once daily, as needed to nostril once daily or if the cap has treat symptoms been left off for five days or longer, by spraying until a fine mist appears. Fluticasone Rx suspension for Perennial nonallergic Perennial Rx suspension: propionate nasal inhalation: rhinitis: nonallergic rhinitis The unit should (FLONASE 50 μg/inhalation Rx suspension: two in children 4 years be primed by ALLERGY RELIEF, (120 sprays) sprays in each nostril of age and older: releasing six fluticasone) once daily or one spray Rx suspension: one sprays until a OTC suspension for in each nostril twice spray in each fine spray nasal inhalation: daily; patients may be nostril once daily; appears before 50 μg/inhalation (30, able to reduce dose to maximum, two initial use and if 60 or 120 sprays) one spray in each nostril sprays in each not used for a once daily for nostril once daily week or more. maintenance therapy Hay fever or other OTC Hay fever or other upper upper respiratory suspension: The respiratory allergies: allergies in children unit should be OTC suspension: two 4 to 11 years of primed by sprays in each nostril age: spraying until a once daily for one week; OTC suspension: fine mist maintenance, one or two one spray in each appears before sprays in each nostril nostril once daily initial use, if not once daily, as needed to used for one treat symptoms week or more, and after cleaning the nozzle. Mometasone Suspension for PAR, SAR: PAR, SAR in The unit should (NASONEX) nasal inhalation: Suspension: two sprays children 2 to 11 be primed Data as of May 22, 2017 YP-U/KS-U/LMR Page 8 of 14

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Usual Dosage Form: Usual Recommended Administration Drug Recommended Strength Adult Dose Considerations Pediatric Dose 50 μg/inhalation in each nostril once daily years old: before initial use (120 sprays) Suspension: one by actuating 10 Nasal polyps in adults spray in each times or until a ≥18 years old: nostril once daily fine spray Suspension: two sprays appears. If in each nostril once or unused for more twice daily than seven days, it should be re-primed by actuating two times or until a fine spray appears. Triamcinolone Rx suspension for SAR and PAR: SAR and PAR in Rx suspension: (triamcinolone, nasal inhalation Rx suspension: two children 6 to 12 The unit should NASACORT (triamcinolone): sprays in each nostril years old: be primed ALLERGY 24HR) 55 μg/inhalation once daily; maintenance, One spray in each before initial use (120 sprays) one spray in each nostril nostril once daily; by releasing five once daily. maximum, two sprays. If not OTC suspension for sprays in each used for more nasal inhalation Hay fever or other upper nostril once daily than two weeks, (NASACORT respiratory allergies: it can be re- ALLERGY 24HR): OTC suspension: two SAR and PAR in primed with one 55 μg/inhalation (30, sprays in each nostril children 2 to 5 spray. 60, or 120 sprays) once daily; maintenance, years old: one inhalation in each One spray in each OTC nostril once daily nostril once daily suspension: The unit should be Hay fever or other primed before upper respiratory initial use and if allergies in children not used for 6 to under 12 more than two years: weeks by OTC Suspension: spraying until a one spray in each fine mist is nostril once daily; produced. maximum, two sprays in each nostril once daily

Hay fever or other upper respiratory allergies in children 2 to under 6 years: OTC Suspension: one spray in each nostril once daily

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SPECIAL POPULATIONS Table 4. Special Populations Population and Precaution Drug Renal Hepatic * Elderly Pediatrics Dysfunction Dysfunction and Nursing Beclomethasone No dosage BECONASE AQ No dosage No dosage Pregnancy adjustment is approved for adjustment adjustment Category C required in the use in children 6 required. required. elderly years of age and Unknown population. older. whether excreted in QNASL is breast milk approved for use in children 4 years of age and older. Budesonide No dosage Approved for Not studied in Not studied in Pregnancy adjustment use in children 6 renal hepatic Category B required in the years of age and dysfunction. dysfunction. elderly older. Excreted in population. breast milk Ciclesonide No dosage OMNARIS is Not studied in No dosage Pregnancy adjustment approved for renal adjustment Category C required in the use in children 6 dysfunction. required. elderly years of age and Unknown population. older for SAR whether and ages 12 excreted in years and older breast milk for PAR.

ZETONNA is approved for use in children 12 years of age and older. Flunisolide No dosage Approved for Not studied in Not studied in Pregnancy adjustment use in children 6 renal hepatic Category C required in the years of age and dysfunction. dysfunction. elderly older. Unknown population. whether excreted in breast milk Fluticasone No dosage Approved for No dosage No dosage Pregnancy furoate adjustment use in children 2 adjustment adjustment Category C required in the years of age and required. required. elderly older. Unknown population. Monitoring is whether recommended excreted in with moderate breast milk and severe hepatic dysfunction.

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Population and Precaution Drug Renal Hepatic Pregnancy* Elderly Pediatrics Dysfunction Dysfunction and Nursing Fluticasone No dosage Approved for Not studied in Not studied in Pregnancy propionate adjustment use in children 4 renal hepatic Category C required in the years of age and dysfunction. dysfunction. elderly older. Unknown population. whether excreted in breast milk Mometasone No dosage Approved for Not studied in No dosage Pregnancy adjustment use in children 2 renal adjustment Category C required in the years of age and dysfunction. required. elderly older for Unknown population. treatment of whether SAR and PAR excreted in (age ≥12 years breast milk for prophylaxis of SAR and age ≥18 years for nasal polyps). Triamcinolone No dosage Approved for No dosage No dosage Pregnancy adjustment use in children 2 adjustment adjustment Category C required in the years of age and required. required. elderly older. Unknown population. whether excreted in breast milk * B = No evidence of risk in humans, but there remains a remote possibility. Animal reproduction studies have failed to demonstrate a risk to the fetus, and there are no adequate and well-controlled studies in pregnant women. Pregnancy Category C = Risk cannot be ruled out. Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

CONCLUSION  Intranasal corticosteroids are used for the management of allergic rhinitis, some forms of nonallergic rhinitis and nasal polyps. They are generally well tolerated and are associated with limited drug interactions due to their localized administration and limited systemic absorption. Like other corticosteroids, intranasal corticosteroids carry warnings regarding use in patients with active infection and the development of signs of , particularly with the administration of higher-than-recommended doses (Wallace et al, 2008).  Intranasal corticosteroids are considered first-line agents for the treatment of allergic rhinitis, especially for patients with moderate to severe symptoms. Consensus guidelines do not recommend the use of one intranasal corticosteroid product over another (Brozek et al, 2010; Seidman et al, 2015; Snellman et al, 2013; Wallace et al, 2008).  All available intranasal corticosteroids have demonstrated safety and efficacy for their respective indications. These agents have been shown to be effective in reducing rhinitis-related nasal symptoms such as congestion, rhinorrhea, sneezing, nasal , and postnasal drip. The differences in tolerability and sensory perceptions noted in clinical trials were minor and did not translate into differences in outcomes. The results of multiple head-to-head trials have generally failed to demonstrate clinically significant differences between products (Aasand et al, 1982; Al-Mohaimeid, 1993; Andersson et al, 1995; Bachert et al, 2004; Bachert et al; 2002; Berger et al, 2003; Day et al, 1998; Drouin et al. 1996; Graft et al, 1996; Gross et al, 2002; Haye et al, 1993; Hebert et al, 1996; LaForce et al, 1994; Langrick, 1984; Lumry et al, 2003; Mak et al, 2013; Mandl et al, 1997; McAllen et al, 1980; McArthur, 1994; Meltzer et al, 2005; Meltzer et al, 2008; Meltzer et al, 2010; Naclerio et al, 2003; Ratner et al, 1992; Sahay et al, 1980; Shah et al, 2003; Sipila et al, 1983; Small et al, 1997; Stern et al, 1997; Stokes et al, 2004; Svendsen et al, 1989; Van As et al, 1993; Vanzieleghem et al, 1987; Varshney et al, 2012; Welsh et al, 1987; Winder et al, 1993).  Two nasal aerosol formulations, beclomethasone (QNASL) and ciclesonide (ZETONNA), have been approved by the FDA for the relief of symptoms associated with PAR and SAR. The other intranasal corticosteroid products are

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formulated as aqueous suspensions, which may be bothersome to patients due to the potential of the suspension to drip down or out of the nose following administration.

REFERENCES  Aasand G, Etholm BO, Skjostad M, Volden J. Flunisolide nasal spray compared to beclomethasone dipropionate in the treatment of seasonal rhinitis. Rhinology. 1982;20(4):205-11.  Al-Mohaimeid H. A parallel-group comparison of budesonide and beclomethasone dipropionate for the treatment of perennial allergic rhinitis in adults. J Int Med Res. 1993;21(2):67-73.  Andersson M, Berglund R, Greiff L, et al. A comparison of budesonide nasal dry powder with fluticasone propionate aqueous nasal spray in patients with perennial allergic rhinitis. Rhinology. 1995;33(1):18-21.  Bachert C, El-Akkad T. Patient preferences and sensory comparisons of three intranasal corticosteroids for the treatment of allergic rhinitis. Ann Allergy Asthma Immunol. 2002;89:292-7.  Bachert C, Lukat KF, Lange B. Effect of intranasal fluticasone propionate and on basal and dynamic measures of hypothalamic-pituitary-adrenal-axis activity in healthy volunteers. 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This information is considered confidential and proprietary to OptumRx. It is intended for internal use only and should be disseminated only to authorized recipients.

 Langrick AF. Comparison of flunisolide and beclomethasone dipropionate in seasonal allergic rhinitis. Curr Med Res Opin. 1984;9:290-5.  Lumry W, Hampel F, LaForce C, et al. A comparison of once-daily triamcinolone acetonide aqueous and twice-daily beclomethasone dipropionate aqueous nasal sprays in the treatment of seasonal allergic rhinitis. Allergy Asthma Proc. 2003;24:203-10.  Mak KK, Ku MS, Lu KH, et al. Comparison of mometasone furoate monohydrate (Nasonex) and fluticasone propionate (Flixonase) nasal sprays in the treatment of dust mite-sensitive children with perennial allergic rhinitis. Pediatr Neonatol. 2013 Aug; 54:239-245. DOI: 10.1016/j.pedneo.2013.01.007.  Mandl M, Nolop K, Lutsky BN. Comparison of once daily mometasone furoate (Nasonex) and fluticasone propionate aqueous nasal sprays for the treatment of perennial rhinitis. The 194-079 Study Group. Ann Allergy Asthma Immunol. 1997:79(3):237-45.  McAllen MK, Portillo PR, Parr EJ, et al. 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 Wallace DV, Dykewicz MS, Bernstein DI, et al. The diagnosis and management of rhinitis: An updated practice parameter of the task force on practice parameters for allergy and immunology. J Allergy Clin Immunol. 2008;122:S1-S84. Available at: http://www.allergyparameters.org/published-practice-parameters/alphabetical-listing/rhinitis-download/. Accessed May 22, 2017.  Welsh PW, Stricker WE, Chu C, et al. Efficacy of beclomethasone nasal solution, flunisolide, and cromolyn in relieving symptoms of ragweed allergy. Mayo Clin Proc. 1987;62:125-34.  Winder J, Bell T, Brodsky L. A comparative study of intranasal triamcinolone acetonide aerosol and intranasal beclomethasone dipropionate aqueous spray in perennial allergic rhinitis. Immunol Allergy Pract. 1993;15(7):203-9.  Yonezaki M, Akiyama K, Karaki M, et al. Preference evaluation and perceived sensory comparison of fluticasone furoate and mometasone furoate intranasal sprays in allergic rhinitis. Auris Nasus Larynx. 2016;43(3):292-7.  ZETONNA prescribing information. Sunovion Pharmaceuticals. Marlborough, MA. October 2014.

Publication Date: May 25, 2017

Data as of May 22, 2017 YP-U/KS-U/LMR Page 14 of 14

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